What is the difference between Unfractionated Heparin (UFH) and Low Molecular Weight Heparin (LMWH)?

From the Guidelines

Unfractionated heparin (UFH) and heparin are essentially the same medication, as "heparin" typically refers to unfractionated heparin. The term "unfractionated" distinguishes it from low molecular weight heparins (LMWHs) like enoxaparin. UFH is a heterogeneous mixture of polysaccharide chains of varying lengths (5,000-30,000 daltons), while LMWHs are derived from UFH through chemical or enzymatic depolymerization, resulting in shorter chains (average 5,000 daltons) 1. UFH requires frequent monitoring via activated partial thromboplastin time (aPTT) and is typically administered intravenously in hospital settings, though subcutaneous administration is possible for prophylaxis. It has a short half-life of 60-90 minutes and works by binding to antithrombin III to inhibit factors Xa and IIa (thrombin) 1. UFH can be completely reversed with protamine sulfate, making it valuable in situations requiring rapid anticoagulation reversal. Its main disadvantages include the need for frequent monitoring, risk of heparin-induced thrombocytopenia, and unpredictable dose response due to binding to plasma proteins and endothelial cells. In contrast, LMWHs have a more predictable dose response and do not require routine monitoring, but their use may be limited in patients with severe renal impairment 1. The choice between UFH and LMWH depends on the individual patient's clinical situation, including the presence of renal impairment, the need for rapid anticoagulation reversal, and the risk of heparin-induced thrombocytopenia. Overall, the decision to use UFH or LMWH should be based on the specific clinical context and the patient's individual needs. Some studies have shown that LMWH is superior to UFH for the treatment of deep vein thrombosis (DVT), particularly for reducing mortality and the risk for major bleeding during initial therapy 1. However, UFH may still be preferred in certain situations, such as in patients with severe renal impairment or those who require rapid anticoagulation reversal. In summary, UFH and LMWH have different advantages and disadvantages, and the choice between them should be based on the individual patient's clinical situation. It is also worth noting that, the most recent study 1 suggests that fixed dose, unmonitored, subcutaneous UFH has been reported to be comparable to LMWH in the treatment of patients with acute VTE.

From the Research

Difference between Unfractionated Heparin and Heparin

• Unfractionated heparin (UFH) is a heterogeneous mixture of glycosaminoglycans that bind to antithrombin via a pentasaccharide, catalyzing the inactivation of thrombin and other clotting factors 2.
• Low-molecular-weight heparin (LMWH) is prepared from standard UFH and has improved bioavailability and a prolonged half-life, which alleviates cumbersome laboratory monitoring and may permit one single daily subcutaneous injection 3.
• The main advantages of LMWH over UFH are its improved efficacy-to-safety ratio, with less bleeding despite similar or improved efficacy 3.
• UFH has unpredictable pharmacokinetic and pharmacodynamic properties due to its binding to endothelial cells, platelet factor 4, and platelets, whereas LMWH has more predictable properties due to its lack of nonspecific binding affinities 2.

Clinical Use and Monitoring

• LMWH has replaced UFH for most clinical indications due to its predictable properties and ease of administration 2.
• However, UFH is still preferred in certain scenarios, such as in patients with creatinine clearance of < 25 mL/min, until further data on therapeutic dosing of LMWHs in renal failure have been published 2.
• The management of heparins is complex and requires frequent laboratory measurements for monitoring, and understanding the characteristics of these anticoagulants is essential to use them safely 4.

Comparative Effectiveness

• Studies have shown that LMWH and UFH have similar effectiveness and cost for venous thromboembolism prophylaxis, but LMWH is associated with fewer complications 5.
• LMWH has also been shown to have a lower incidence of heparin-induced thrombocytopenia (HIT) and HIT complicated by venous thromboembolism compared to UFH in postoperative patients 6.